Effect of acute scurvy on the guinea-pig heart

EFFECT. OF ACUTE SCURVY ON THE GUINEA-PIG HEART JOSEPHINE McBROOM, Pxu.D. DOUGLAS A, SUNDERLAND, M.D. JOHN R. MOTE, M.D. AND lr. DUCKETT JONES, M.D. BOSTON Rinehart and Mettier + and Rinehart, Connor and Mettier 2 reported | in a condition of scurvy with a concurrent streptococcic fection exhibit degenerative and proliferative lesions on the heart lves and in the synovial and periarticular tissues of various joints. compared these lesions to those of rheumatic fever and hypothesized that the latter disease may be a response of scorbutic tissue treptococcic infection. Schultz * corroborated their results in part. these results several points may be mentioned which make it ppear that the lesions may be the effect of scurvy on the heart. First, can be determined from the reports, the pathologic changes arently occurred with equal frequency in both the animals that had acute and those that had chronic or subacute scurvy with superimposed infection. Second, according to the protocols given, the animals which were on a diet productive of a chronic or a subacute scorbutic ondition and which had a superimposed streptococcic infection exhibited it autopsy some of the gross findings of acute scurvy. The same ype of lesions, but of lesser degree, were described as observed in the animals with acute and chronic scorbutic conditions without infection. Since it is improbable that clinical acute rheumatic fever is a condition of acute scurvy, it is considered desirable to determine whether From the House of the Good Samaritan. The expenses of this study have been defrayed by a grant from the Commonwealth Fund. 1. Rinehart, J. F., and Mettier, S. R.: Am. J. Path. 10:61, 1934. 2. Rinehart, J. F.; Connor, C. L., and Mettier, S. R.: J. Exper. Med. 59:97, 1934 3. Schultz, M. P.: Arch. Path. 21:472, 1936. McBROOM ET AL-GUINEA-PIC HEART or not the lesions described Pig heart. In view of the are the result of acute scurvy in the work of Wolbach and Howe * on the nature ot pathologic conditions j due to a deficiency of vi Cit vy be expected that lesions similar to those described might occur areas of severe stress or injury to the interstitial connective tissue < These lesions are not considered by us to be identical with, or even closely related to, those of acute rheumatic fever in human beings It is our Purpose in this paper to give the results of a study o the effect of scurvy on the guinea-pig heart both in the absence and in the presence of concurrent streptococcic infection. METHOD Diet —The scurvy-inducing diet of Wolbach and Howe* was used. sists of: soy beans soaked over night, sterilized in autoclave 15 fc r minutes and mashed, 50 Gm.: rolled oats, 29 Gm.; butter, 5 Gm.: Fle yeast, 4 Gm.; dried milk (Klim), 10 Gm.; calcium carb nate, 1 a sodium chloride, 1 Gm. The ingredients are moistened, mixed thoroughly and spread in thin sheets to dry. Each guinea-pig was given 20 Gm. of the crumbled mixture daily, with filter paper for filler. In addition, each animal received 1 cc. of cod liver oil daily by medicine dropper. All animals were fed this basic diet plus 8 cc. of orange juice daily for one week, to accustom them to the before the start of an experiment. The orange juice was wit n from all save the controls at this time. This diet produced definite ( curvy usually within from fifteen to twenty days, and if it was continued, death usually resulted within from twenty to forty days. Wolbach and Howe‘ and Wolbach 5 have reported on the effectiveness of this diet in producing a condition of total scurvy. The diet productive of chronic scorbutic lesions given certain animals indi cated below, consisted of the Wolbach diet plus 2 cc. of strained oran juice given by medicine dropper on every third day. This amount of the source of vitamin C was sufficient to maintain the weight of the animal and to cause no or only very slight gradual decrease in the red blood cell count and hemoglobin over } a period of weeks. The deficiency did, however, prevent the normal rate of growth in the young, growing 300 to 400 Gm. animals used in this experiment. The semi scorbutic diet administered to animals as listed in the table consisted of the diet productive of chronic scurvy with short periods of the diet causing acute scorbutic lesions. This was fed to determine whether variations in the severity of the deficiency might induce differences in the nature of the lesions. 4. Wolbach, S. B., and Howe, P. R.: Arch. Path. 1:1, 1926. 5. Wolbach, S. B.: Am. J. Path. 9:689, 1933. 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Note edema and fragmentation o leaflet. There is minimal proliferative reaction. Fig. 2 (guinea-pig 8, basal diet to death on twenty-second day) .—Mitral valve; hematoxylin and eosin stain; X 35. The valve is generally thickened. The darker area to the left represents acute valvulitis with hemorrhage and polymorphonuclear leukocytic and lymphocytic infiltration. Fig. 3 (guinea-pig 5, basal diet to death on twenty-first day).—Mitral valve; hematoxylin and eosin stain; X 30. The valve is definitely thickened with a proliferative nodule at the line of closure. Fig. 4 (guinea-pig 5, basal diet to death on twenty-first day).—Mitral valve; hematoxylin and eosin stain; X 200. This is a high power view of a proliferative nodule at the line of closure of the valve. Note the proliferation of endothelial and subendothelial cells. Phagocytic cells, lymphocytic and other mononuclear cells are distinguishable. Fig. 5 (guinea-pig 7, basal diet to death on twenty-fourth day).—Mitral valve; hematoxylin and eosin stain; X 30. Note the definite small proliferative nodule at the line of closure. The general thickening and edema are minimal. Fig. 6 (guinea-pig 7, basal diet to death on twenty-fourth day).—Mitral valve; hematoxylin and eosin stain; < 150. Note the proliferative nodule at the valve’s line of closure. The nodular character is definite, with proliferation of subendothelial and stroma cells. A few lymphocytes are present. Figure 1 26 ARCHIVES OF PATHOLOGY EXPLANATION OF PLATE 2 Fig. 1 (guinea-pig 6, basal diet to death on forty-first day).—DMitral valve; hematoxylin and eosin stain; 30. There is a marked proliferative nodular reaction at the line of closure on each valve leaflet. This is more definite on the right. Fig. 2 (guinea-pig 6, basal diet to death on forty-first day) —Mitral valve; hematoxylin and eosin stain; > 150. Fibroblastic proliferation is present, and some collagen change and débris are distinguishable. Lymphocytic infiltration is evident, as is edema of the valve stroma at the lower end of the figure. Fig. 3 (guinea-pig 8, basal diet to death on twenty-second day).—Mitral valve; hematoxylin and eosin stain; X 30. There is marked edema of the entire valve stroma with definite thickening of the valve and an acute reaction at the line of closure. Fig. 4 (guinea-pig 8, basal diet to death on twenty-second day).—Mitral valve; hematoxylin and eosin stain; X 150. The acute valvulitis and proliferative reaction at the line of closure are evident. Edema and the poor structure of the collagen are well demonstrated. Lymphocytic and phagocytic cell infiltration may be made out with ease. Fig. 5—Normal aortic valve; hematoxylin and eosin stain; < 50. McBROOM ET AL—GUINEA-PIG HEART IN SCURVY bo N Figure 2 28 ARCHIVES OF PATHOLOGY EXPLANATION Or PLATE 3 Fig. 1 (guinea-pig 3, basal diet to death on twenty-fifth day).—Mitral valve; matoxylin and eosin stain; X 125. There is marked edema of the valve (lower A slight lymphocytic reaction of the whole area is present. Fig. 2 (guinea-pig 10, basal diet to death on forty-fourth day ).—Myocardium ; hematoxylin and eosin stain; X 250. Myocardial degeneration is well demonstrated, as is some edema. The cellular reaction is not marked and is almost entirely limited to large mononuclear cells of undifferentiated type with some phagocytic wandering cells, Fig. 3 (guinea-pig 20, semiscorbutic diet to death on sixty-seventh day with added streptococcic infection as indicated in table) —Mitral valve; hematoxylin and eosin stain 3 X 440. A high magnification of a nodule showing endothelial and subendothelial proliferation. This is an unusually marked reaction of the type. Fig. 4 (guinea-pig 21, diet and infection as in table) —Mitral valve; X 150. Increased thickness of the valve is apparent, as is the nodular area of cellular proliferation and infiltration. The cells involved are endothelial lining cells and underlying fibroblasts, with an infiltration of lymphocytes and phagocytic wandering cells. :